Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of anti-inflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved.
Pyrazole compounds have been used in the treatment of inflammation. For example, U.S. Pat. No. 4,146,721 to Rainer describes 1,3-diarylpyrazole-4-acetic acid as having anti-inflammatory, antipyretic and sedative uses. U.S. Pat. No. 4,914,121 to Sawai et al describes 1,3-diarylpyrazole-4-acetic acid as having immune control uses.
Canadian Patent No. 1,130,808 describes 1,3-diphenyl pyrazoles and 1,5 diphenyl pyrazoles, including compounds having a phenyl ring optionally substituted at the 1 position with methyl, chloro or methoxy. These compounds are mentioned as having anti-inflammatory, analgesic and anti-pyretic properties.
EP No. 554,829, published Aug. 11, 1993, describes 1,5-diaryl pyrazoles and 1,3-diaryl pyrazoles as having anti-inflammatory activity.
Netherlands Patent No. 7,112,377 describes 1,5-diphenyl pyrazoles substituted at the "3" position with carboxylic acid derivatives. Such compounds are reported to have analgesic and anti-inflammatory activity.
U.S. Pat. No. 5,164,381 to Wachter et al describes 1,5-diphenyl pyrazole compounds which are reported to alleviate inflammation. Propanoic acid derivatives are the position "3" substituents.
U.S. Pat. No. 5,051,518 to Murray et al describes a family of (1'-methoxyphenyl-5'-aryl-3'-pyrazolyl)-N-hydroxypropanamide derivatives as being cyclooxygenase and lipoxygenase inhibitors. Pyrazole compounds, where haloalkyl radicals are the 3'-substituents, are also reported as intermediates.
U.S. Pat. No. 5,134,142 to Matsuo et al describes 1,5-diaryl pyrazoles, and specifically, 1-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl pyrazole, as having anti-inflammatory activity.